Biology subjects

Zhou, Q.

Publications and source records attributed to Zhou, Q..

At least 19 recordsLinked to original sources

bioRxiv2026

High-content imaging of live microglia-containing Alzheimer's disease brain organoids

Alzheimer's disease (AD) is the most common progressive neurodegenerative disease for which there is currently no safe and effective treatment. AD is characterized by the pathological aggregation of amyloid-{beta} (A{beta}) in the brain resulting in neuronal dysfunction/death and cognitive decline. Modeling these processes in vitro remains challenging due to the lack of an immune-competent 3D in vitro human model of AD amenable to high-throughput analyses. Conventional cerebral organoids (COs) lack microglia and are optically dense which precludes real-time longitudinal analyses. Here, we employ the fluorescent amyloid probe PyrPeg to selectively monitor A{beta} aggregation, and calcein AM and propidium iodide to assess cellular viability within microglia-containing COs (MCOs). We identify age-dependent DS-AD-associated phenotypes within T21 MCOs including A{beta} neuropathology, neurodegeneration, and glial cell dysregulation. Our platform supports real-time, multiplexed tracking of disease progression and provides a scalable platform for longitudinal analyses studying disease mechanisms and targeted approaches to treatment.

neuroscience↗

bioRxiv2026

HIV-1 Integrase C-terminal Domain Mutations Regulate ALLINI Sensitivity

HIV-1 integrase (IN) performs two essential functions in virus replication: catalyzing the integration of reverse-transcribed viral cDNA into host DNA and promoting proper virion maturation. The latter is mediated by IN binding to the genomic RNA (gRNA) through basic residues in its C-terminal domain (CTD), thereby ensuring correct repackaging of the gRNA inside the remodeled capsid lattice. Allosteric integrase inhibitors (ALLINIs) bind within a V-shaped pocket at the interface of the catalytic core domain (CCD) of IN dimers, promote the engagement of the CTDs from adjacent dimers, and thereby occlude gRNA binding. However, virological evidence supporting a role for the IN-CTD in ALLINI mechanism of action is lacking, as mutations in CTD residues implicated in ALLINI-induced multimerization typically yield non-infectious viruses. Here we demonstrate that IN-CTD mutants bearing compensatory substitutions that restore infectivity exhibit markedly altered sensitivity to ALLINIs. Specifically, we show that R269A/K273A substitutions within the IN-CTD confer ~100-fold enhanced sensitivity to ALLINIs. This correlates with a loss of IN-gRNA binding at low ALLINI concentrations, while exerting minimal effects on IN multimerization in vitro and in virions. In contrast, we found that the IN I268T substitution which arose as a suppressor mutation of I268A confers partial resistance to ALLINI-induced inhibition of gRNA binding. Collectively, these findings provide the first direct genetic evidence that CTD residues, despite being distal to the primary drug binding site at the CCD dimer, modulate sensitivity to ALLINIs and highlights IN-gRNA binding as a central target of ALLINIs.

microbiology↗

bioRxiv2026

TFL1 homolog integrates temperature signals to control timing of developmental transitions in woodland strawberry

In overwintering plants of temperate climates, inflorescence and flower buds commonly form in autumn under cool temperatures, while flowering occurs the following spring. However, how cool temperatures regulate inflorescence and flower development remains poorly understood. We used woodland strawberry (Fragaria vesca L.), a perennial Rosaceae herb, to investigate the effects of cool temperature on reproductive development. We characterized temperature-dependent developmental patterns at macroscopic and microscopic scale and combined time- and stage-specific gene expression analyses. We show that cool temperature accelerates floral transition but subsequently slows inflorescence and flower development, causing increased inflorescence branching, higher floral organ numbers, and berry fasciation. These effects were restricted to the apical inflorescence and flower meristems, whereas higher-order meristems remained unaffected. Expression analyses revealed stage- and temperature-dependent changes in the abundance and spatial distribution of TERMINAL FLOWER1 (FvTFL1) encoding the floral repressor. Loss of functional FvTFL1 abolished temperature-dependent differences in floral transition, inflorescence branching, and floral organ numbers. Our results establish FvTFL1 as a major regulator of temperature-responsive reproductive development. The stage-specific activity of FvTFL1 provides a mechanism through which woodland strawberry integrates temperature signals to balance developmental plasticity of the primary growth axis with the robustness of lateral branches.

plant biology↗

bioRxiv2026

Ourotide: decoding the hierarchical peptide recognition for generative design

The historical dichotomy between small-molecule pocket and extended protein interfaces misrepresents the physical reality of peptide recognition.1,2 Here we show that peptide binding is not a simple structural intermediate but a distinctly multimodal landscape comprising small-molecule-like pockets, protein-like interfaces, and a previously unrecognized third mode. This third regime is governed by a hierarchical subpocket architecture where a flattened surface achieves near-complete peptide engagement through spatially partitioned hydrophobic components. To maintain stability, an incompletely enclosed dominant anchor cooperates with highly hydrated auxiliary subpockets and an asymmetric receptor coupling mechanism that concentrates energy in an adjacent continuous water network. Because this unique binding mode suffers from extreme data scarcity, standard deep learning models fail to capture its physics.3,4 To resolve this, we mapped these specific geometric signatures to mine structurally faithful training distributions from global protein interactomes. Based on these data, we trained Ourotide, a deep learning framework coupling conditional geometric flow matching with interface-aware affinity learning. Evaluated across peptides up to 65 residues, Ourotide outperforms generalist models in backbone accuracy, interface recovery, and affinity prediction. This approach suggests that overcoming data scarcity in the physical sciences requires physics-guided data augmentation rather than naive statistical scaling.

bioinformatics↗

bioRxiv2026

Ecologically inspired assembly of a Bacillales synthetic community for lignin degradation

Lignin remains a major bottleneck in biomass valorization due to its heterogeneous and recalcitrant structure. Traditionally, lignin degradation has been developed using a single-microorganism or single-enzyme approach, with efforts focused on identifying ligninolytic activities of individual bacteria or fungi. Here, we establish a framework for designing lignin-degrading synthetic microbial communities (SynComs) by integrating top-down ecological filtering with bottom-up trait-based selection. This approach enables the selection of bacteria with ligninolytic capacity while retaining community members that form strong biofilms and contribute indirectly to overall community function. Proteomic profiling uncovered lignin-driven functional reprogramming of the SynCom, highlighting strain-specific enzymatic specializations that collectively enable lignin depolymerization. Our work highlights the potential of SynComs for lignin degradation and shows how rationally designed, functionally partitioned communities can enhance lignin conversion.

microbiology↗

bioRxiv2026

An orally administered peptide hydrogel disentangles immune-microbiota crosstalk for long-term ulcerative colitis therapy

Ulcerative colitis (UC) is a global health challenge driven by immune dysregulation and gut microbiota imbalance.1 Current treatments, limited by insufficient efficacy and systemic toxicity during prolonged use, fail to resolve the intertwined immune-microbial pathology.2 Here, we report an orally administered self-assembled hydrogel C2-(IIRR)2I-NH2 (CIR), engineered from host defense peptides, which disrupts the immune-microbiota entanglement. The CIR hydrogel exhibits structural transformation at the inflamed sites rich in liposaccharide (LPS), a pro-inflammatory molecule derived from pathogenic bacteria. Stable {beta}-sheet nanofibers can transfer to bioactive -helix conformations, enabling localized therapeutic action with minimal off-target toxicity. In murine colitis models, CIR restores mucosal integrity and suppresses disease severity, outperforming the first-line drug 5-aminosalicylic acid (5-ASA). Microbiome profiling reveals its capacity to rebalance gut microbiota, depleting LPS produced pathogenic bacteria like Prevotellaceae. Transcriptomic analyses further indicate that CIR silences TLR4-mediated signaling pathway. By synergistically targeting immune dysregulation and microbial dysbiosis, this self-assembled peptide hydrogel establishes a paradigm-shifting strategy for UC, offering clinically translatable potential for multifactorial gastrointestinal disorders.

bioengineering↗

bioRxiv2026

Global transmission architecture of VIM carbapenemases reveals host-specific dissemination strategies

Carbapenemase-producing Gram-negative bacteria carrying Verona integron-encoded metallo-{beta}-lactamase (VIM) pose a persistent global threat, yet the mechanisms driving their worldwide dissemination remain poorly resolved. We analysed 5,617 blaVIM-positive genomes collected from 73 countries or regions across six continents between 1999 and 2025 to reconstruct the global epidemiology and transmission architecture of VIM carbapenemases. Forty VIM variants were identified across 16 bacterial genera, revealing marked host preferences and temporal shifts. VIM-2 dominated global circulation, whereas VIM-1 and VIM-4 remained prominent among Enterobacterales. Strikingly, VIM spread followed distinct host-specific evolutionary strategies. In Pseudomonas aeruginosa, dissemination was largely clone-driven, with high-risk lineages ST111 and ST235 supporting long-term persistence through lineage expansion and stable inheritance. By contrast, Enterobacterales were dominated by horizontal transmission through broad-host-range IncHI2A, IncA, and IncC plasmids, although only a limited subset of plasmid-VIM combinations achieved intercontinental spread. Among 2,828 loci with sufficient flanking sequence, 96.2% were embedded within integrative genetic elements, frequently nested with insertion sequences and phage-related elements, revealing a multilayered mobile-element network underlying VIM persistence. Structural analyses showed a highly conserved metallo-{beta}-lactamase scaffold but recurrent diversification near substrate-interacting residues, particularly positions 224 and 228. Shared genetic clusters between human-associated and environmental isolates further suggested cross-niche circulation. Together, these findings establish a hierarchical, host-dependent framework for global VIM dissemination, integrating clonal expansion, plasmid transfer, and nested mobile genetic elements. ImportanceBy analysing 5,617 blaVIM-positive genomes worldwide, this study reveals a host-dependent transmission architecture of VIM carbapenemases. In P. aeruginosa, VIM dissemination is mainly driven by expansion of successful high-risk clones, particularly ST111 and ST235, whereas in Enterobacterales it is primarily mediated by broad-host-range plasmids enabling cross-species transfer. Global VIM spread is not driven by a single dominant pathway but by a limited number of successful clone-plasmid-mobile element combinations, while most genetic backgrounds remain regionally restricted. These findings define a hierarchical transmission model of VIM evolution and provide insights for genomic surveillance and targeted control of metallo-{beta}-lactamase-mediated antimicrobial resistance.

microbiology↗

bioRxiv2026

Association of Sleep with Anxiety in Chinese Empty-Nest Older Adults: The Mediating Roles of Physical Exercise and Social Participation

Sleep disturbances are common among older adults and are often closely associated with anxiety symptoms, which together can substantially compromise physical and mental health.A cross-sectional analysis was conducted using data from the 2017/2018 wave of the Chinese Longitudinal Healthy Longevity Survey (CLHLS). The study included 6,106 Chinese older adults (aged [≥]65 years) living in empty-nest households. Physical exercise was measured based on self-reported regular engagement in exercise, and social participation was defined as involvement in organized social activities (e.g., community or group-based events). Associations between sleep quality and duration and anxiety were estimated using multivariable logistic regression, and mediation effects of physical exercise and social participation were tested using bootstrap resampling.Among the 6,106 participants, 593 (9.7%) reported anxiety symptoms. Multivariable logistic regression analysis indicated that poor sleep quality was significantly associated with a higher risk of anxiety (OR = 3.23, 95% CI: 2.62-4.01, P < 0.001). Short sleep duration was also an independent risk factor for anxiety (OR = 1.34, 95% CI: 1.04-1.74, P = 0.025), whereas long sleep duration showed no significant association. Subgroup analyses stratified by sex, marital status, and economic status consistently revealed significant associations between sleep (both quality and duration) and anxiety, with no statistically significant interactions observed. Mediation analyses demonstrated that physical exercise significantly mediated the relationships of both sleep quality and long sleep duration with anxiety (all P < 0.01, with bootstrap confidence intervals excluding zero). Similarly, social participation significantly mediated the relationships of both short and long sleep duration with anxiety (all P < 0.01, with bootstrap confidence intervals excluding zero).In Chinese empty-nest older adults, both poor sleep quality and short sleep duration are independent risk factors for anxiety symptoms, with sleep quality exerting a stronger influence. Physical exercise partially mediated the associations between sleep quality and anxiety and between long sleep duration and anxiety, whereas social participation mediated the association between sleep duration (short and long) and anxiety. Improving sleep quality and ensuring adequate sleep duration may help reduce anxiety risk, and interventions promoting physical exercise and social participation could enhance these protective effects.

immunology↗

bioRxiv2026

Coronary Artery Disease Transcriptomics Reveals Two Drivers of the Endothelial Cell SR-BI Expression and LDL Transport that Underlie Atherosclerosis

Atherosclerosis is initiated by circulating low-density lipoprotein (LDL) cholesterol transfer into the artery wall, which is mediated by scavenger receptor class B, type I (SR-BI) in endothelial cells(1). Employing single-cell RNA sequencing in human coronary artery disease (CAD) samples, here we show that endothelial SR-BI expression is increased in atheroma, and in endothelial cells with a transcript signature indicative of responding to disturbed blood flow. In vivo in mice hypercholesterolemia and disturbed blood flow independently upregulate endothelial SR-BI; the flow-related upregulation initiates endothelial cell LDL uptake and atherogenesis. Guided by transcription factor networks, it is revealed that HIF-1 binding to human Scarb1 Intron 1 governs endothelial SR-BI transcription, and in mice HIF-1 drives hypercholesterolemia-related SR-BI upregulation and artery LDL uptake. Thus, the two major instigators of atherosclerotic lesion formation, hypercholesterolemia and disturbed blood flow, both upregulate endothelial SR-BI to drive the LDL transport that underlies the disorder. Targeting the processes regulating endothelial SR-BI potentially represents a new therapeutic strategy against CAD.

cell biology↗

bioRxiv2026

Characterizing Functional Clusters of V4 Neurons in Digital Twins

Neurons in primate visual cortical area V4 display tuning for multiple visual features, including color, shape, texture, and depth. Whether and how these neurons are organized into functional architectures remains largely unknown. Using two-photon calcium imaging in anesthetized macaques, we recorded responses of hundreds of V4 neurons to natural images and used these data to train deep convolutional neural network models (digital twins), obtaining synthetic images (SI) that maximized neuronal responses. Based on their SIs, these neurons clustered into classes that spatially matched the orientation, color, and curvature maps from intrinsic signal imaging. Furthermore, lesion study in digital twins revealed different integration rules for different neuron classes. Thus, digital twins of V4 neurons can be applied as a promising tool to characterize neurons fundamental features, which underlie the functional clustering in this area. HighlightsO_LINeurons in V4 are examined with two-photon calcium imaging and DCNN modeling (digital twins) C_LIO_LISynthetic images derived from neurons digital twins reveal distinct neuron groups C_LIO_LIThese groups match functional types defined by intrinsic signal optical imaging C_LIO_LILesion study in digital twins demonstrates neural mechanisms underlying feature tuning C_LI

neuroscience↗

bioRxiv2026

Hidden genetic diversity in 320 nearly-complete East Asian genome assemblies

East Asian populations, representing over 20% of the global population, remain critically underrepresented in human genomic studies, limiting our understanding of population-stratified genetic variation and its implications for health and disease. Here we present the first phase of the Asian Pan-Genome project (APG), comprising 320 nearly complete, fully phased haploid genome assemblies from 160 East Asian individuals. These assemblies achieve unprecedented quality, with an average contig N50 of 144.3 megabase pairs and an average quality value of 64.5. Leveraging these superior assemblies, we reveal previously uncharacterized diversity in human repeatome, including population-stratified patterns in centromere satellites and rDNA arrays. Compared to existing global human genome assemblies, the newly generated genomes supplement 152 million base pairs of novel sequences, 355 gene gains, 18,300 structural variation loci and 26 large euchromatic inversions missing from current human pangenomes. We perform population stratification analyses of structural variations, and further resolve the structural haplotypes of complex genomic regions such as Major Histocompatibility Complex and Survival Motor Neuron loci across global pangenomes, exemplifying tandem-duplicate and inversion-rich complex locus architectures in the human genome, respectively. This resource provides a critical foundation for human genetic studies, especially for East Asian populations, promoting more accurate variant discovery, reducing bias, and ultimately advancing the equity and efficacy of genomic medicine.

genomics↗

bioRxiv2026

A Promoter Competition Hub Orchestrates Runx1 Alternative Promoter Usage during Skeletal Muscle Stem Cell Activation

Alternative promoter (AP) usage profoundly expands transcriptomic and proteomic diversity, yet the regulatory principles governing promoter choice remain poorly understood. Here, using the dual-promoter Runx1 locus as a paradigm in skeletal muscle stem cells (MuSCs), we uncover a promoter competition hub that orchestrates AP selection during MuSC fate transition from activation to proliferation. We find antagonistic expression dynamics between the two Runx1 promoters, with the primary promoter (PP) active in the early activating stage and the secondary promoter (SP) induced later in proliferation. Combinatorial genetic perturbations in vitro and in vivo establish the non-redundant roles of PP- and SP-derived isoforms in MuSC lineage progression. Mechanistically, we find that PP and SP engage in reciprocal competition in a multi-connected enhancer-promoter (E-P) loop hub. Further dissection identifies a cohort of key enhancers that dynamically interact with PP/SP to orchestrate the competition. Moreover, we establish the transcription factor USF1 as a key factor driving the dynamic E-P interactions and PP/SP competition. Beyond Runx1, high-resolution Micro-C reveals promoter competition as a general mechanism regulating a subset of AP choices in MuSC activation/proliferation. Collectively, our study uncovers a dynamic promoter competition hub that governs AP selection in MuSC lineage progression, offering fundamental insights into how 3D genome architecture coordinates precise, stage-specific gene expression programs during cell fate transitions.

genetics↗

bioRxiv2026

Spatial Topology Reveals Biologically Distinct Recurrent Motifs in Colorectal Cancer

Most spatial transcriptomic analyses of solid tumors focus on individual cell states or single-sample spatial domains rather than on recurrent multicellular tissue architectures shared across patients, and typically depend on predefined cell-type annotations or compartment definitions. We developed STORM (Spatial Topology analysis of Recurrent Motifs), an unsupervised graph-attention variational autoencoder that learns recurrent spatial motifs directly from cell-level graph structure and molecular profiles without cell-type labels, manual annotation, or predefined compartments. We applied to 32 Xenium sections from 16 patients with paired early-onset (EOCRC) and average-onset (AOCRC) colorectal cancer, STORM identified 10 recurrent motifs that self-organized into tumor-parenchymal, stromal, and immune macro-compartments. Among these, the Desmoplastic Fibrotic Barrier (DFB) motif, a CAF- and ECM-rich boundary architecture, was associated with restricted CD8+ T-cell geodesic access to tumor cores independently of CD8+ abundance, as demonstrated by abundance-normalized neighborhood enrichment statistics and within-sample mixed-effects models. EOCRC selectively amplified this barrier-exclusion architecture, exhibiting tighter tumor parenchyma, denser DFB shells, and a DFB-specific ECM activation program that yielded an age-specific prognostic signature in TCGA-COAD. Translation of motif macro-classes to H&E images via a Vision Transformer classifier produced an image-derived DFB-barrier composite that predicted overall survival in advanced-stage TCGA colorectal cancer. STORM provides an annotation-free framework for discovering recurrent spatial motifs and identifies a fibroblast barrier architecture whose topological association with immune exclusion is independent of effector abundance, amplified in early-onset disease, and translatable to a deployable pathology-based prognostic biomarker.

bioinformatics↗

bioRxiv2026

A nitrite-responsive regulatory RNA locus sustains commensal resilience against nitrosative stress

Commensal microbes in the gastrointestinal tract are central to host health, yet they must adapt to frequent perturbations such as intestinal inflammation that challenges microbial homeostasis. A major challenge during inflammation is exposure to host-derived reactive nitrogen species (RNS), which damage macromolecules and impair microbial fitness, but how commensals orchestrate defense against nitrosative stress remains poorly defined. Here, we show that Bacteroides thetaiotaomicron mounts a protective RNS-defense program centered on the hybrid cluster protein Hcp, which is required for fitness under nitrosative stress. We identify a nitrite-responsive SnoA locus (Stress-responsive Nitric Oxide regulator A) that promotes HcpR-dependent hcp expression. In vivo, this pathway promotes commensal resilience in both an antibiotic-perturbed, Nos2-dependent model of intestinal nitrosative stress and during Salmonella-induced gut inflammation. Together, our findings identify a regulatory pathway that enables a dominant gut commensal to withstand host-derived nitrosative stress and persist during intestinal inflammation.

microbiology↗

bioRxiv2026

New genes play a prominent role in evolution of new sperm classes of Drosophila

The widespread and regulated production of infertile parasperm assisting fertilization of eusperm provides a compelling model for elucidating the mechanisms of cellular innovation and altruism. Here we identify two specific parasperm lineages in Drosophila pseudoobscura that are segregated in development from the eusperm lineage by their single-cell transcriptomes. Most X-linked genes, except for species-specific new genes, show testis-specific repressive epigenetic modifications and become downregulated upon meiotic entry, supporting meiotic X chromosome inactivation. Between sperm classes, nearly half of the known meiotic arrest genes and their downstream targets are differentially transcribed, with over 200 genes displaying a gradient of transcription levels correlated with that of tail lengths. New genes are overrepresented throughout the hierarchical regulatory network of sperm divergence and over 60% of them exhibit a new cell-level expression compared to their parental copies. These results together indicate that new genes play a prominent role in the emergence of low-cost parasperm that shield the eusperm until fertilization.

evolutionary biology↗

bioRxiv2026

CellOS: Learning a World Model of Cellular State through Joint Embedding Prediction

Foundation models learned from single-cell transcriptomes are central to the prospect of AI virtual cell that can represent, query and predict cellular state. However, most current single-cell foundation models learn from a single view of gene expression and are optimized primarily through reconstruction or next-token prediction. As a result, they capture expression abundance but cannot explicitly reconcile complementary views of cellular state. Here we present CellOS, a multi-view foundation model that learns cellular representations from paired expression and perception views. CellOS integrates complementary views through a scalable three-stage training strategy that combines causal cell-sentence language modelling, function-preserving dense-to-mixture-of-experts expansion and latent-space alignment via an LLM-JEPA objective. Using this framework, we trained a 12-billion-parameter model on 390.5 million single-cell transcriptomes. Across diverse benchmarks spanning cell-state annotation, batch integration and perturbation-response prediction, CellOS consistently outperformed state-of-the-art single-cell foundation models. Together, these results suggest that predictive alignment between complementary cellular views provides a scalable path toward representation-centric cellular world models and transferable AI virtual cells.

bioinformatics↗

bioRxiv2026

(2R,6R)-Hydroxynorketamine elicits rapid antidepressant effects by promoting astrocytic μ-δ opioid receptor heterodimerization

Ketamine produces rapid antidepressant effects but is constrained by psychotomimetic properties and abuse potential. The ketamine metabolite (2R,6R)-hydroxynorketamine (HNK) shows antidepressant-like efficacy without N-methyl-D-aspartate receptor (NMDAR) blockade, yet its upstream targets remain unclear. Here we show that HNK potentiates hippocampal excitatory transmission and reverses stress-induced behavioural deficits through opioid receptor signaling. Pharmacological and genetic analyses reveal a requirement for both {micro}- and {delta}-opioid receptors in astrocytes. Chronic stress reduces {micro}-{delta} receptor heterodimers in the hippocampus, and a single dose of HNK restores their abundance. PAINT-MINFLUX nanoscopy quantifies increased {micro}-{delta} heterodimerization, and molecular dynamics simulations indicate selective binding of HNK to the {micro}-receptor protomer via Asp147 and Tyr148. Mutating these residues abolishes HNK-driven heterodimer formation, downstream signaling and rapid antidepressant-like effects in vivo. Astrocytic {micro}-{delta} opioid receptor heterodimers thus represent a targetable mechanism for next-generation rapid-acting antidepressants.

neuroscience↗

bioRxiv2026

Biosynthetic allene and alkyne formation by enzymatic prenyl demethylation

Allenes and alkynes are versatile functional groups in total synthesis, medicinal chemistry, and bioorthogonal conjugation. The biosynthetic logic of how Nature installs allene or alkyne in natural products, especially that of allenes, is not well understood. Here we uncovered allenes and alkynes can be formed enzymatically through oxidative C(sp2)-demethylation of the common five-carbon prenyl group. Two fungal cytochrome P450 monooxygenases, PpnB and NseB, from the penipratynolene and sinuxylamide biosynthetic pathways, respectively, were shown to catalyze oxidative removal of a C(sp2)-methyl group in O-prenyl-L-tyrosine to afford O-homoallenyl-L-tyrosine and O-but-2-ynyl-L-tyrosine, respectively. Combining density functional theory calculations, heterologous expression, biotransformation and enzymatic assays with isotopically labeled substrates, a mechanism involving selective C-C bond cleavage followed by product-determining hydrogen atom abstraction is presented. An additional P450 enzyme from the penipratynolene pathway, PpnD, acts as an oxidative isomerase that converts the four-carbon terminal allene into a terminal alkyne. This unprecedented enzymatic editing strategy to install allene and alkyne expands the catalytic repertoire of P450 enzymes. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=100 SRC="FIGDIR/small/727785v1_ufig1.gif" ALT="Figure 1"> View larger version (21K): org.highwire.dtl.DTLVardef@54a57dorg.highwire.dtl.DTLVardef@13cb5d0org.highwire.dtl.DTLVardef@c4a2b7org.highwire.dtl.DTLVardef@196b357_HPS_FORMAT_FIGEXP M_FIG C_FIG

biochemistry↗